Model: Repeat screening for syphilis in pregnancy

Congenital syphilis (CS) occurs via vertical transmission of syphilis during pregnancy. In infants born with CS, the infection can lead to growth restriction and long-term sequelae, including neurological impairment, bone deformities, and hearing loss. Screening for syphilis is currently offered later in pregnancy (in the first trimester) as part of the NHS Infectious Diseases in Pregnancy Screening programme. This project assesses whether an additional screen for syphilis should be offered in the third trimester of pregnancy. In 2020, the UK National Screening Committee (UK NSC) reviewed repeat screening and commissioned a cost-effectiveness model comparing universal third-trimester repeat screening with a single first-trimester screen. At that time, UK data on maternal syphilis incidence/prevalence and CS incidence were limited, requiring estimates from other sources. The 2020 analysis concluded that universal repeat screening was unlikely to be cost-effective at a willingness-to-pay threshold of £20,000–£30,000 per QALY, although results were sensitive to incidence assumptions (Aquarius Population Health, 2020). In 2024 the UK NSC received a request through the joint annual call submission from NHS England and the UK Health Security Agency to revise the cost-effectiveness analysis, as recent increases in syphilis incidence and in CS cases have been observed and UK data collected by the Integrated Screening Outcomes Surveillance Service (ISOSS) is now available. The Sheffield Evidence Network for Screening Synthesis (SENSS) will appraise the 2020 model and update its structure, parameters and evidence base. We will assess whether the prior model can be transparently reconstructed in Excel and identify where updated assumptions or restructuring are required (e.g., infection acquisition between screens, treatment effectiveness and timing, real-world care pathways and costs, and outcomes by gestational age). ISOSS data will be used where feasible to inform maternal syphilis incidence, screening uptake, test performance, pregnancy and infant outcomes (supplemented where appropriate by national perinatal surveillance sources), late presentation of CS, and treatment volumes. Where ISOSS is incomplete (e.g., missing stratification by screening status or incident vs prevalent infection), we will undertake targeted searches of peer-reviewed and grey literature, including modelling studies published since the most recent systematic review (Zhang et al., 2024). Cost inputs will be updated using NHS tariffs, the BNF and PSSRU indices. The updated model will adopt a lifetime time horizon and generate incremental costs, QALYs and CS outcomes for the recommended base case. We will conduct one-way deterministic and probabilistic sensitivity analyses, as well as scenario testing to characterise parameter and structural uncertainty, including incidence and uptake thresholds relevant to UK implementation. References: Aquarius Population Health (2020) Repeat screening for syphilis in pregnancy as an alternative screening strategy in the UK: a cost-effectiveness analysis. Prepared for the UK National Screening Committee. Commissioned by Public Health England. Retrieved August 1, 2025, from UK National Screening Committee website: https://view-health-screening-recommendations.service.gov.uk/syphilis/ Zhang, M., Zhang, H., Hui, X., Qu, H., Xia, J., Xu, F., Shi, C., He, J., Cao, Y. and Hu, M., 2024. The cost-effectiveness of syphilis screening in pregnant women: a systematic literature review. Frontiers in Public Health, 12, p.1268653.